Our work focuses on the molecular events involved in malignant transformation and the control of cellular proliferation. Normal cells often cease division under conditions in which malignant cells continue to divide. A major goal of our work is the description of the biochemical pathways that lead nonproliferating cells to proceed through the cell cycle. Thus, the stimulation of cell division by growth factors, by tumor-promoting phorbol esters, or by the expression of transforming gene products is under study. Many of the key proteins that participate in the early steps are located in the plasma membrane or cytoplasm of the cell. We are attempting to determine the nature of the signals transmitted to the nucleus that result in cell division. Reversible protein phosphorylation appears to be important in regulating some of these early biochemical events. Therefore, the potentially relevant protein kinases, phosphoprotein phosphatases, and their substrates are purified and characterized.